A phase Ib/II, multicenter, open label, study of LEE011 in combination with MEK162 in adult patients with NRAS mutant melanoma
- Conditions
- malignant cutaneous melanomaskin cancer10040900
- Registration Number
- NL-OMON44775
- Lead Sponsor
- Array Biopharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NRAS mutant melanoma (written documentation)
2. ECOG performance status of 0 * 1.
3. Phase Ib: evaluable disease only is allowed. For phase II expansion at least one measurable lesion as defined by RECIST 1.1.
4. Archival of fresh tumor biopsy specimen (if no archival tumor) for all patients.
5. A tumor biopsy at time of study entry and on day C1D15 in the phase II part of the study.
6. A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy
and the first dose of study drugs:
* > 2 weeks for systemic antineoplastic therapy or any experimental therapy
* > 6 weeks for nitrosoureas and mitomycin-C).
* * 4 weeks for biologic therapy (e.g., antibodies)
7. Laboratory values:
a. Absolute Neutrophil Count (ANC) * 1.5 x 109/L.
b. Hemoglobin (Hgb) * 9 g/dL (5,58 mmol/L)
c. Platelets * 75 x 109/L without tranfusions within 21 days before 1st treatment.
d. PT/INR and aPTT * 1.5 ULN
e. Serum creatinine *1.5 ULN.
f. Serum total bilirubin * 1.5 x upper limit of normal (ULN).
g. AST and ALT * 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT * 5 x ULN.
8. A negative serum pregnancy test * 72 hours before starting study treatment
1. Presence of any brain metastases detected by MRI or CT of the brain at screening.
2. Uncontrolled arterial hypertension despite medical treatment
3. Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the
absorption of LEE011 or MEK162.
4. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
* Left ventricular ejection fraction (LVEF) * 50%
* Congenital long QT syndrome or family history of unexpected sudden cardiac death,
* QTcF or QTcB >450 ms for males and >470 ms for females at screening,
* Angina pectoris or acute myocardial infarction * 3 months prior to starting study drug, clinically significant bradycardia, history or presence of ventricular tachyarrhytmia, unstable atrial fibrillation, complete left bundle branch block, obligate use of pacemaker or implantable cardioverter defibrillator
5. Treatment with agents that are known to cause QTc prolongation.
6. Treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window. Agents that are known strong inducers or inhibitors CYP3A4 are prohibited. Enzyme inducing anti-epileptic drugs are not permitted.
7. Patients with concurrent severe and/or uncontrolled concurrent medical conditions
8. Major surgery <2 weeks before starting study treatment.
9. Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C
10. Current evidence of retinal disease; history of CSR, RVO or ophthalmology as assessed
by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO.
11. Pregnant or nursing (lactating) women.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase Ib: Incidence of Dose Limiting Toxicities (DLT)<br /><br>Phase II: Overall Response Rate (CR and PR) according to RECIST 1.1</p><br>
- Secondary Outcome Measures
Name Time Method <p>Phase Ib: Plasma concentration-time profiles of LEE011 and MEK162, PK parameters<br /><br>Phase II: Duration of response (DOR), Time to progression (TTP), Progression<br /><br>Free Survival (PFS), Overall Survival (OS) and Best Overall<br /><br>Response (BOR) according to RECIST 1.1<br /><br><br /><br>Both phase Ib and phase II: Incidence and severity of adverse drug reactions<br /><br>and serious adverse drug reactions. Changes in hematology and chemistry values,<br /><br>vital signs, ECGs, and dose interruptions, dose reduction and dose intensity.</p><br>